The catabolism of antitumor alkaloids found in Vinca rosea will be investigated as a search for new antitumor drugs, as an aid to elucidating the structure-activity relationships among the known oncolytic alkaloids from the plant, and as a research thrust into the currently obscure area of secondary natural product catabolism and function. This work will be attacked with a known biosynthetic precursor, in a H-3 and C-14 labeled form, to enable the screening-out of false catabolites of the particular alkaloids, since only those catabolites with the same H-3: C-14 ratio as that of the precursor will be selected as true catabolites. Full structural characterization of the catabolites and eventual testing of their oncolytic activity will be done to construct a catabolic pathway for the Vinca alkaloids and to examine structure-activity relationships. The biosynthesis of the dimeric, indole-indoline alkaloids of V. rosea will be investigated on the basis of the incorporation of tryptophan and stereospecifically labeled loganin by radiochemical labeling techniques. Depending on the initial results, possible syntheses of suspected intermediates in the biosynthesis and testing of their actual role may be sought. The sequential biosynthetic interrelationship of these alkaloids will also be examined by means of C-14 CO2 labeling studies. The biosynthesis of camptothecin, a potential antitumor alkaloid from Camptotheca acuminata, will be investigated via a hypothesis adapted from work of E. Wenkert. Tryptophan, loganin, vincoside, and other putative precursors, including the quinoline analogs of vincoside, etc., will be validated or eliminated as constituents of the biosynthetic pathway to camptothecin. Stereochemical requirements of the intermediates will be ascertained.